Variant 3-161246403-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015938.5(NMD3):c.1085G>C(p.Arg362Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,371,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

NMD3
NM_015938.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.25

Variant links:

Genes affected

NMD3 (HGNC:24250): (NMD3 ribosome export adaptor) Ribosomal 40S and 60S subunits associate in the nucleolus and are exported to the cytoplasm. The protein encoded by this gene is involved in the passage of the 60S subunit through the nuclear pore complex and into the cytoplasm. Several transcript variants exist for this gene, but the full-length natures of only two have been described to date. [provided by RefSeq, Feb 2016]

NMD3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMD3	NM_015938.5 linkuse as main transcript	c.1085G>C	p.Arg362Pro	missense_variant	12/16	ENST00000351193.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NMD3	ENST00000351193.7 linkuse as main transcript	c.1085G>C	p.Arg362Pro	missense_variant	12/16	1	NM_015938.5	P1
NMD3	ENST00000472947.5 linkuse as main transcript	c.1085G>C	p.Arg362Pro	missense_variant	12/17	1
NMD3	ENST00000460469.1 linkuse as main transcript	c.1085G>C	p.Arg362Pro	missense_variant	11/15	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.29e-7

AC:

AN:

1371312

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

676942

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.53e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.1085G>C (p.R362P) alteration is located in exon 12 (coding exon 11) of the NMD3 gene. This alteration results from a G to C substitution at nucleotide position 1085, causing the arginine (R) at amino acid position 362 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.24

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

T;.;T

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Pathogenic

3.3

M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-6.2

D;D;D

REVEL

Uncertain

0.60

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.026

D;D;D

Polyphen

0.038

B;P;B

Vest4

0.88

MutPred

0.68

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);

MVP

0.76

MPC

0.12

ClinPred

1.0

GERP RS

5.0

Varity_R

0.92

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over